Providence, RI—The use of a CAC score (CACS) might not be the best way to assess the risk of atherosclerosis in smokers, according to a recent retrospective study.

CACS, derived from computed tomography, helps clinicians predict the likelihood of cardiovascular events or mortality. But researchers from Brown University in Providence point out that HMG-CoA-reductase inhibitors, better known as statins, might also increase coronary calcification.

That is especially a problem because of the widespread use of statins to reduce cardiovascular events, according to a recent report in PLoS One. The authors sought to determine the likelihood of severe CACS with the use of regular statin therapy.

To do that, they conducted a retrospective, case-control study of 1,181 U.S. veterans without coronary artery disease (CAD) from a single site, the Providence, Rhode Island VA Medical Center. With the duration of statin therapy for primary prevention divided into 5-year groups, the primary outcome was defined as CACS derived from low-dose lung-cancer screening computed tomography (LCSCT). Results were stratified by CACs severity (none = 0; mild = 1-99; moderate = 100-399; and severe ≥400 AU). Included in the adjustment models were atherosclerotic cardiovascular disease (ASCVD) risk score, BMI, and chronic kidney disease (glomerular filtration rate of <60 mL/min/1.73 m2).

Of the patients who had a mean age of 64.7 ± 7.2 years, the majority, 60%, were prescribed a statin at baseline. Results indicated that the duration of statin therapy was associated with greater odds of having increased CACS:

• 0-5 years, OR: 1.71 [CI: 1.34-2.18], P <.001
• Less than 5-10 years, OR: 2.80 [CI: 2.01-3.90], P <.001
• Greater than 10 years, OR: 5.30 [CI: 3.23-8.70], P <.001.

The relationship between statin duration and CACS remained significant after multivariate adjustment (>0-5 years, OR: 1.49 [CI: 1.16-1.92], P = .002; >5-10 years, OR: 2.38 [CI: 1.7-3.35], P <.001; >10 years, OR: 4.48 [CI: 2.7-7.43], P <.001), the researchers pointed out.

“Long-term use of statins is associated with increased likelihood of severe CACS in patients with significant smoking history,” the study concludes. “The use of CACS to interpret cardiovascular event risk may require adjustment in the context of chronic statin therapy.”

The authors write that “coronary artery disease (CAD) due to calcific atherosclerosis is a major cause of morbidity and mortality worldwide. Measures of increased atherosclerotic plaque calcification have been predictive of coronary artery disease burden, cardiovascular events, and all-cause mortality. Moreover, an increasing rate of progression of the calcification in the coronary vasculature has been associated with worsening prognosis and increased adverse events.”

Recent research has demonstrated evidence “supporting the association between increased density of calcification in atherosclerotic plaques and more stable disease,” they add.

The study describes how statins have shown success at reducing the risk of cardiovascular events and, as a result, have become the current standard of care in patients at moderate-to-elevated cardiovascular risk. The drugs were originally developed as cholesterol-lowering agents, but multiple studies found that statin therapy reduced the risk of myocardial infarction out of proportion to the lipid-lowering effect.

“While statins impact atherosclerotic plaque lipid burden, the exact effect of statin therapy on coronary artery calcification has been less clear,” according to the researchers. “Some initial reports suggested that statin use either reduced calcification or slowed the progression of atherosclerotic calcification, while others indicated statin use resulted in little to no change in the progression of calcification. More recently, a growing number of studies have demonstrated the impact of statin use to be associated with increasing measures of coronary artery calcification.”

The research piggybacked on LCSCT screening to acquire coronary calcification data without the need for additional radiation exposure.

The authors conclude that “long-term duration of time on statin therapy is associated with the likelihood of having severe CACS in patients who have sufficient smoking history to qualify for lung cancer screening. These findings highlight an important complexity to the relationship between statin therapy and CACS, indicating that risk from CACS should be interpreted not just in the context of traditional cardiovascular risk factors and serial CACS progression, but also in the context of plaque-altering treatment.”

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